Funded by NIH in 2008 and 2013, the Colorado Clinical and Translational Sciences Institute (CCTSI) at the University of Colorado Denver (CU-D) has taken impressive steps to transform and improve the biomedical; research and training enterprise in the Colorado region and to accelerate and catalyze the translation of discoveries into improved patient care and public health. The CCTSI, a partnership of CU-D, CU Boulder (CU- B), Colorado State University (CSU), six hospitals and 20 community organizations, has established new infrastructure, streamlined processes and expanded existing resources and services for investigators and stakeholders; tripled the number of training and education programs supporting development of a translational workforce; administratively centralized and expanded the breadth of clinical research capacity and expertise; established system-wide informatics capabilities; promoted team science and interdisciplinary research; established an extensive community engagement program and enhanced research across the lifespan; streamlined processes and reduced start-up times for trials; created an academic home for clinical & translational scientists and trainees; and actively engaged in CTSA network activities. Despite these successes, there remain many challenges to accelerating the translational research process locally and nationally. This application maps our path forward to meet these challenges. Through 2018 CTSA funding, we will develop new methods, innovations, expertise, and procedures to: a) achieve a new level of measurable performance in training translational teams, b) improve efficiency and quality of the full spectrum of translational research, c) facilitate multi-site clinical trials, d) engage regional communities and stakeholders as partners, and e) collaborate and disseminate best practices into the national CTSA consortium to accelerate the translation of discoveries into improved health and patient care. We will accomplish these objectives by embracing the following five Overall Strategic Goals: Goal 1: Develop, educate and sustain a diverse translational science workforce to ensure highest research innovation, quality and safety. Goal 2: Create a translational research environment in which team science and collaboration both locally and nationally are facilitated, supported and valued. Goal 3: Engage local and national communities and stakeholders in all phases of the translational research process. Goal 4: Create novel methodologies and resources to support and integrate research in special populations, including children, the elderly, the underserved and those with rare diseases. Goal 5: Further innovate and streamline our processes and enhance our informatics capacity for research start-up, implementation and oversight to promote quality, efficiency, & safety of our research and our active participation in the national CTSA Trial Innovation Network. Special efforts will be made to enhance diversity in our workforce. Our progress will be monitored by our Evaluation Core and we will make mid-course corrections as needed to achieve these goals and ultimately improve the health of our state and the nation.